Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Genetic Factors in Type 2 Diabetes: The End of the Beginning?
Stephen O'Rahilly,1*Inês Barroso,2Nicholas J. Wareham3
The intensive search for genetic variants that predispose totype 2 diabetes was launched with optimism, but progress hasbeen slower than was hoped. Even so, major advances have beenmade in the understanding of monogenic forms of the diseasewhich together represent a substantial health burden, and afew common gene variants that influence susceptibility havenow been unequivocally identified. Armed with a better understandingof the tools needed to detect such genes, it seems inevitablethat the rate of progress will increase and the relevance ofgenetic information to the diagnosis, treatment, and preventionof diabetes will become increasingly tangible.
1 University of Cambridge, Department of Clinical Biochemistry, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK. 2 The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambs CB10 1SA, UK. 3 Medical Research Council Epidemiology Unit, Elsie Widdowson Laboratory, Fulbourn Road, Cambridge CB1 9NL, UK.
* To whom correspondence should be addressed. E-mail: so104{at}medschl.cam.ac.uk
A truncation mutation in TBC1D4 in a family with acanthosis nigricans and postprandial hyperinsulinemia.
S. Dash, H. Sano, J. J. Rochford, R. K. Semple, G. Yeo, C. S. S. Hyden, M. A. Soos, J. Clark, A. Rodin, C. Langenberg, et al. (2009)
PNAS
106, 9350-9355
|Abstract »|Full Text »|PDF »
Genetic Variation in KCNQ1 Associates With Fasting Glucose and{beta}-Cell Function: A Study of 3,734 Subjects Comprising Three Ethnicities Living in Singapore.
J. T. Tan, S. Nurbaya, D. Gardner, S. Ye, E. S. Tai, and D. P.K. Ng (2009)
Diabetes
58, 1445-1449
|Abstract »|Full Text »|PDF »
Mid- and Late-Life Diabetes in Relation to the Risk of Dementia: A Population-Based Twin Study.
W. Xu, C. Qiu, M. Gatz, N. L. Pedersen, B. Johansson, and L. Fratiglioni (2009)
Diabetes
58, 71-77
|Abstract »|Full Text »|PDF »
Mycobacterial Clearance from Sputum Is Delayed during the First Phase of Treatment in Patients with Diabetes.
B. I. Restrepo, S. P. Fisher-Hoch, B. Smith, S. Jeon, M. H. Rahbar, J. B. McCormick, and the Nuevo Santander Tuberculosis Trackers (2008)
Am J Trop Med Hyg
79, 541-544
|Abstract »|Full Text »|PDF »
Role of the Transcription Factor Sox4 in Insulin Secretion and Impaired Glucose Tolerance.
M. Goldsworthy, A. Hugill, H. Freeman, E. Horner, K. Shimomura, D. Bogani, G. Pieles, V. Mijat, R. Arkell, S. Bhattacharya, et al. (2008)
Diabetes
57, 2234-2244
|Abstract »|Full Text »|PDF »
Association of CDKAL1, IGF2BP2, CDKN2A/B, HHEX, SLC30A8, and KCNJ11 With Susceptibility to Type 2 Diabetes in a Japanese Population.
S. Omori, Y. Tanaka, A. Takahashi, H. Hirose, A. Kashiwagi, K. Kaku, R. Kawamori, Y. Nakamura, and S. Maeda (2008)
Diabetes
57, 791-795
|Abstract »|Full Text »|PDF »
Disruption of the striated muscle glycogen-targeting subunit of protein phosphatase 1: influence of the genetic background.
J. Paterson, I. R Kelsall, and P. T W Cohen (2008)
J. Mol. Endocrinol.
40, 47-59
|Abstract »|Full Text »|PDF »
Association between KCNJ11 E23K genotype and cardiovascular and glucose metabolism phenotypes in older men and women.
Y. Yi, L. Dongmei, D. A. Phares, E. P. Weiss, J. Brandauer, and J. M. Hagberg (2008)
Exp Physiol
93, 95-103
|Abstract »|Full Text »|PDF »
Comparing Diabetes Prevalence Between African Americans and Whites of Similar Socioeconomic Status.
L. B. Signorello, D. G. Schlundt, S. S. Cohen, M. D. Steinwandel, M. S. Buchowski, J. K. McLaughlin, M. K. Hargreaves, and W. J. Blot (2007)
Am J Public Health
97, 2260-2267
|Abstract »|Full Text »|PDF »
Is Family History a Useful Tool for Detecting Children at Risk for Diabetes and Cardiovascular Diseases? A Public Health Perspective.
R. Valdez, K. J. Greenlund, M. J. Khoury, and P. W. Yoon (2007)
Pediatrics
120, S78-S86
|Abstract »|Full Text »|PDF »
Metabolic homeostasis and tissue renewal are dependent on {beta}1,6GlcNAc-branched N-glycans.
P. Cheung, J. Pawling, E. A Partridge, B. Sukhu, M. Grynpas, and J. W Dennis (2007)
Glycobiology
17, 828-837
|Abstract »|Full Text »|PDF »
Analysis of Genetic Variation in Akt2/PKB-{beta} in Severe Insulin Resistance, Lipodystrophy, Type 2 Diabetes, and Related Metabolic Phenotypes.
K. Tan, W. A. Kimber, J. Luan, M. A. Soos, R. K. Semple, N. J. Wareham, S. O'Rahilly, and I. Barroso (2007)
Diabetes
56, 714-719
|Abstract »|Full Text »|PDF »
Lamin A/C Polymorphisms, Type 2 Diabetes, and the Metabolic Syndrome: Case-Control and Quantitative Trait Studies.
J. L. Mesa, R. J.F. Loos, P. W. Franks, K. K. Ong, J. Luan, S. O'Rahilly, N. J. Wareham, and I. Barroso (2007)
Diabetes
56, 884-889
|Abstract »|Full Text »|PDF »
Phenotypic characterization of polygenic type 2 diabetes in TALLYHO/JngJ mice..
J. H. Kim, T. P Stewart, M. Soltani-Bejnood, L. Wang, J. M Fortuna, O. A Mostafa, N. Moustaid-Moussa, A. M Shoieb, M. F McEntee, Y. Wang, et al. (2006)
J. Endocrinol.
191, 437-446
|Abstract »|Full Text »|PDF »
A combined 1H-NMR spectroscopy- and mass spectrometry-based metabolomic study of the PPAR-{alpha} null mutant mouse defines profound systemic changes in metabolism linked to the metabolic syndrome.
H. J. Atherton, N. J. Bailey, W. Zhang, J. Taylor, H. Major, J. Shockcor, K. Clarke, and J. L. Griffin (2006)
Physiol Genomics
27, 178-186
|Abstract »|Full Text »|PDF »
Environmental Cardiology: Studying Mechanistic Links Between Pollution and Heart Disease.
Association Analysis of 6,736 U.K. Subjects Provides Replication and Confirms TCF7L2 as a Type 2 Diabetes Susceptibility Gene With a Substantial Effect on Individual Risk.
C. J. Groves, E. Zeggini, J. Minton, T. M. Frayling, M. N. Weedon, N. W. Rayner, G. A. Hitman, M. Walker, S. Wiltshire, A. T. Hattersley, et al. (2006)
Diabetes
55, 2640-2644
|Abstract »|Full Text »|PDF »
TCF7L2 polymorphisms and progression to diabetes in the Diabetes Prevention Program..
J. C. Florez, K. A. Jablonski, N. Bayley, T. I. Pollin, P. I.W. de Bakker, A. R. Shuldiner, W. C. Knowler, D. M. Nathan, D. Altshuler, and the Diabetes Prevention Program Research Group (2006)
N. Engl. J. Med.
355, 241-250
|Abstract »|Full Text »|PDF »
Genetic variants and common diseases--better late than never..
S. O'Rahilly and N. J. Wareham (2006)
N. Engl. J. Med.
355, 306-308
|Full Text »|PDF »
Computational disease gene identification: a concert of methods prioritizes type 2 diabetes and obesity candidate genes.
N. Tiffin, E. Adie, F. Turner, H. G. Brunner, M. A. van Driel, M. Oti, N. Lopez-Bigas, C. Ouzounis, C. Perez-Iratxeta, M. A. Andrade-Navarro, et al. (2006)
Nucleic Acids Res.
34, 3067-3081
|Abstract »|Full Text »|PDF »
Haplotype Structures and Large-Scale Association Testing of the 5' AMP-Activated Protein Kinase Genes PRKAA2, PRKAB1, and PRKAB2 With Type 2 Diabetes.
M. W. Sun, J. Y. Lee, P. I.W. de Bakker, N. P. Burtt, P. Almgren, L. Rastam, T. Tuomi, D. Gaudet, M. J. Daly, J. N. Hirschhorn, et al. (2006)
Diabetes
55, 849-855
|Abstract »|Full Text »|PDF »
Contribution of regulatory and structural variations in APOE to predicting dyslipidemia.
J. H. Stengard, S. L. R. Kardia, S. C. Hamon, R. Frikke-Schmidt, A. Tybjaerg-Hansen, V. Salomaa, E. Boerwinkle, and C. F. Sing (2006)
J. Lipid Res.
47, 318-328
|Abstract »|Full Text »|PDF »
Insulin Resistance Syndrome in Subjects With Mutated RING Finger Protein TRIM37.
N. Karlberg, H. Jalanko, J. Kallijarvi, A.-E. Lehesjoki, and M. Lipsanen-Nyman (2005)
Diabetes
54, 3577-3581
|Abstract »|Full Text »|PDF »
Phosphatase and Tensin Homolog Regulation of Islet Growth and Glucose Homeostasis.
J. A. Kushner, L. Simpson, L. M. Wartschow, S. Guo, M. M. Rankin, R. Parsons, and M. F. White (2005)
J. Biol. Chem.
280, 39388-39393
|Abstract »|Full Text »|PDF »
Sequence Variation in PPARG May Underlie Differential Response to Troglitazone.
J. K. Wolford, K. A. Yeatts, S. K. Dhanjal, M. H. Black, A. H. Xiang, T. A. Buchanan, and R. M. Watanabe (2005)
Diabetes
54, 3319-3325
|Abstract »|Full Text »|PDF »
Diabesity: A Polygenic Model of Dietary-Induced Obesity from Ad Libitum Overfeeding of Sprague-Dawley Rats and Its Modulation by Moderate and Marked Dietary Restriction.
K. P. Keenan, C.-M. Hoe, L. Mixson, C. L. Mccoy, J. B. Coleman, B. A. Mattson, G. A. Ballam, L. A. Gumprecht, and K. A. Soper (2005)
Toxicol Pathol
33, 650-674
|Abstract »|Full Text »|PDF »
Association Testing of the Protein Tyrosine Phosphatase 1B Gene (PTPN1) With Type 2 Diabetes in 7,883 People.
J. C. Florez, C. M. Agapakis, N. P. Burtt, M. Sun, P. Almgren, L. Rastam, T. Tuomi, D. Gaudet, T. J. Hudson, M. J. Daly, et al. (2005)
Diabetes
54, 1884-1891
|Abstract »|Full Text »|PDF »